The role of allergy or localized intestinal anaphylaxis in acute and chronic intestinal inflammation is not known. This primarily reflects our lack of a sensitive, highly specific marker for enteric immediate hypersensitivity. This project will seek to identify such a marker by measuring the release of histamine and prostaglandins from intestinal mucosa in response to antigen challenge. Initial studies will be performed in vivo in established rat and guinea pig models of intestinal anaphylaxis. The release of histamine and prostaglandins will be correlated to the dose of antigen employed, the serum and tissue levels of reagin, the release of intestinal goblet cell mucin, and histologic evidence for mucosal injury, cellular infiltration, or local mast cell degranulation. Inhibition of the anaphylactic response will be attempted by use of blocking antibodies and by specific inhibitors of mast cell mediators. To facilitate application to human bowel biopsy specimens, in vitro organ culture of sensitized animal bowel will be undertaken with an emphasis on basal and antigen-stimulated release of mast cell mediators. The effect of co-incubation with blocking antibodies and specific inhibitors will be determined. To control for non-anaphylactic mediator release, biopsies of resected bowel from patients with ischemic or inflammatory disease will be studied in vitro in organ culture. In the third phase of the study, human intestinal mucosal biopsies will be challenged by specific and control antigens in organ culture. We will seek evidence to either confirm or refute a role for the immediate hypersensitivity response in conditions such as gluten-sensitive enteropathy, eosinophilic gastroenteritis, "allergic" enteropathy, and inflammatory bowel disease.